Abstract
The accumulation of protein aggregates is thought to be an important component in the pathogenesis of mutant SOD1-induced disease. Mutant SOD1 aggregates appear to be cleared by proteasomes, at least in vitro, suggesting a potentially important role for proteasome degradation pathways in vivo. G93A SOD1 transgenic mice show an increase in proteasome activity and induction of immuno-proteasome subunits within spinal cord as they develop neurological symptoms. To determine what role immuno-proteasomes may have in mutant SOD1-induced disease, we crossed G93A SOD1 transgenic mice with LMP2-/- mice to obtain G93A SOD1 mice lacking the LMP2 immuno-proteasome subunit. G93A SOD1/LMP2-/- mice show significant reductions in proteasome function within spinal cord compared to G93A SOD1 mice. However, G93A SOD1/LMP2-/- mice show no change in motor function decline, or survival compared to G93A SOD1 mice. These results indicate that the loss of immuno-proteasome function in vivo does not significantly alter mutant SOD1-induced disease.
Original language | English (US) |
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Pages (from-to) | 53-58 |
Number of pages | 6 |
Journal | Experimental Neurology |
Volume | 206 |
Issue number | 1 |
DOIs | |
State | Published - Jul 2007 |
Keywords
- ALS
- Aggregation
- Astrocyte
- Microglia
- Motor neuron
- Spinal cord
ASJC Scopus subject areas
- Neurology
- Developmental Neuroscience